The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases...

The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain

..2% in granule cells, and is not present in cancer cell lines. hmdC is a constituent of nuclear DNA that is highly abundant in the brain, suggesting a role in epigenetic control of neuronal function...

Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification

Shinsuke ItoHoward Hughes Medical InstituteNature 466:1129-33. 2010

..Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification...

..Therefore, Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning...

Chun Xiao SongDepartment of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USANat Biotechnol 29:68-72. 2011

..We also find a gene expression level-dependent enrichment of intragenic 5-hmC in mouse cerebellum and an age-dependent acquisition of this modification in specific gene bodies linked to neurodegenerative disorders...

..of a family of DNA hydroxylases that possess enzymatic activity toward the methyl mark on the 5-position of cytosine (5-methylcytosine [5mC]), a well-characterized epigenetic modification that has essential roles in regulating ..

The behaviour of 5-hydroxymethylcytosine in bisulfite sequencing

Yun HuangDepartment of Pathology, Harvard Medical School and Immune Disease Institute, Boston, Massachusetts, United States of AmericaPLoS ONE 5:e8888. 2010

DNA methylation is a major epigenetic mechanism for gene silencing. Whereas methyltransferases mediate cytosine methylation, it is less clear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether ..

..Our study suggests that, although the conversion of 5mC to 5hmC in zygotes is an enzyme-catalyzed process, loss of 5hmC during preimplantation appears to be a DNA replication-dependent passive process...

Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine

Genome-wide erasure of DNA cytosine-5 methylation has been reported to occur along the paternal pronucleus in fertilized oocytes in an apparently replication-independent manner, but the mechanism of this reprogramming process has remained ..

..We show that these enzymes introduce a double-stranded cleavage at the 3'-side away from the recognized modified cytosine. The distances between the cleavage sites and the modified cytosine are fixed within a narrow range, with the ..

..The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development...

Current evidence indicates that methylation of cytosine in mammalian DNA is restricted to both strands of the symmetrical sequence CpG, although there have been sporadic reports that sequences other than CpG may also be methylated...

..In addition, a lack of 5hmC may become a useful biomarker for cancer diagnosis...

Cytosine methylation and the ecology of intragenomic parasites

J A YoderDepartment of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USATrends Genet 13:335-40. 1997

..gene control; instead, suppression of parasitic sequence elements appears to be the primary function of cytosine methylation, with crucial secondary roles in allele-specific gene expression as seen in X inactivation and ..

5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells

..There is growing evidence that TET proteins, which convert 5-methylcytosine (5mC) to 5hmC, play important biological roles. To further understand the function of 5hmC, an analysis of the genome-wide localization of this mark is required...

b>Cytosine methylation in CpG dinucleotides is believed to be important in gene regulation, and is generally associated with reduced levels of transcription...

Epigenetic regulation of HIV-1 latency by cytosine methylation

Steven E KauderGladstone Institute of Virology and Immunology, San Francisco, California, United States of AmericaPLoS Pathog 5:e1000495. 2009

..MBD2 and histone deacetylase 2 (HDAC2) are found at one of these CpG islands during latency. Inhibition of cytosine methylation with 5-aza-2'deoxycytidine (aza-CdR) abrogates recruitment of MBD2 and HDAC2...

..We propose that some amounts of transiently stable 5hmCs may indicate a poised epigenetic state or demethylation intermediate, whereas others may suggest a locally accessible chromosomal environment for the TET enzymatic apparatus...

..stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethyl-cytosine (hmC) by the action of 2-oxoglutarate- and Fe(ii)-dependent oxygenases of the TET family...

Over the past few decades, DNA methylation at the 5-position of cytosine (5-methylcytosine, 5mC) has emerged as an important epigenetic modification that plays essential roles in development, aging and disease...

Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered...

Genetic and functional diversification of small RNA pathways in plants

Zhixin XieCenter for Gene Research and Biotechnology and Department of Botany and Plant Pathology, Oregon State University, Corvallis, USAPLoS Biol 2:E104. 2004

..We conclude that proliferation and diversification of DCL and RDR genes during evolution of plants contributed to specialization of small RNA-directed pathways for development, chromatin structure, and defense...

..The AlkB enzyme couples oxidative decarboxylation of alpha-ketoglutarate to the hydroxylation of these methylated bases in DNA, resulting in direct reversion to the unmodified base and the release of formaldehyde...

Examination of the specificity of DNA methylation profiling techniques towards 5-methylcytosine and 5-hydroxymethylcytosine

..Here we report a systematic study of the effects of five different forms of cytosine in DNA on mammalian and yeast RNA polymerase II transcription, providing new insights into potential functional ..

..Our results suggest that there is little genetic change in the S(0) generation of resynthesized B. napus polyploids. In contrast, DNA methylation was altered extensively in a pattern that indicates tight regulation of epigenetic changes...

Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for a mechanism of carcinogenesis

..In this larger series with extended follow up, intermediate dose cidofovir without probenecid for the treatment of BKVAN continues to show stabilization of renal function without progression to renal failure...

The distribution of cytosine methylation in 6.2 Mb of the mouse genome was tested using cohybridization of genomic representations from a methylation-sensitive restriction enzyme and its methylation-insensitive isoschizomer...

..It is now recognized that gene expression can be regulated by epigenetic modifications including cytosine methylation within the promoter region, specifically cytosines adjacent to guanosine nucleotides (CpG islands)...

..DNA methylation is the epigenetic process by which a DNA methyltransferase (DNMT) enzyme covalently modifies cytosine dinucleotides within a gene's promoter region via addition of a methyl group, resulting in changes in ..

..at our institution, to comprehensively characterize and make available the global epigenetic patterns of cytosine methylation in a single population of human hematopoietic (CD34+) stem cells isolated from umbilical cord blood ..

..code, consist fundamentally of DNA methylation of CpG-dinucleotides, which occurs at the fifth position of the cytosine pyrimidine ring, and regulation of chromatin structure through post-translational modification of histones...

..identifying sequence variation in the promoter region of precursor microRNAs and their target genes involved in cytosine methylation and histone modification and evaluate their association with gene methylation and lung cancer...

..The best studied epigenetic mechanism is DNA methylation, the covalent addition of a methyl group to a cytosine residue occurring mostly in a CpG site (i.e., DNA sequence with a cytosine next to a guanine)...

..In mammalian cells, DNA methylation occurs primarily as symmetrical methylation of cytosine in the context of the dinucleotide CpG, and the presence of high levels of 5-methyl- cytosine (5mC) at promoters ..

..will test the role of Vitamin C as a potential co-factor of Tet enzymes in the generation of 5-hydroxymethyl-Cytosine at the promoters of germline genes;2) to determine the functional consequences of exposure to Vitamin C in ..

..Our exciting preliminary data reveal that the newly described epigenetic modification implicated in cytosine demethylation, 5-hydroxymethyl-cytosine (5-hmC), has a profound effect upon the ability of Z versus R to induce ..

Project Summary/Abstract Cytosine DNA methylation is an epigenetic mark for gene silencing that is important in many gene regulatory systems including mammalian imprinting, X-chromosome inactivation, and the silencing of transposons and ..

..Many environmental carcinogens deaminate bases in DNA. Of these bases, deamination of cytosine to uracil is of particular importance because human mitDNA is rich in cytosine and uracil mispairs with guanine ..

..Recent studies have demonstrated that CSR is initiated by AID-catalyzed DNA cytosine deamination events and that the resulting uracil residues are recognized and processed by ubiquitous DNA repair ..